A combinatorial synthesis of tyrphostins via the “directed sorting” method

✍ Scribed by Shuhao Shi; Xiao-yi Xiao; Anthony W. Czarnik

• Book ID: 101241549
• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 153 KB
• Volume: 61
• Category: Article
• ISSN: 0006-3592
• DOI: 10.1002/(sici)1097-0290(199824)61:1<7::aid-bit4>3.0.co;2-n

✦ Synopsis

Using solid-phase organic synthesis, we have prepared a 432-member (18 × 8 × 3) sample library based on the AG 490 ''tyrphostin'' template. By utilizing 432 reactors each equipped with a unique radiofrequency memory ID tag, the 432 products could be obtained as discrete entities (i.e., not as mixtures) via 18 + 8 + 3, or 29 reactions. Reading each ID tag after each reaction step permitted the ''directed sorting'' of reactors into appropriate reaction vessels containing multiple reactors. After synthesis, all products were cleaved from the solid-phase support and lyophilized to afford powders. Characterization of 5% of the library members by NMR and mass spectrometry provided verification of structure. In addition, TLC analysis of every library member provided evidence that most (or all) are composed of a single major organic compound. Some 88% of these samples were obtained in amounts of between 5 and 19 mg. Using this reaction sequence and the ''directed sorting'' approach, the synthesis of much larger AG 490-based libraries can be envisioned. ©